Angiotensin II receptors and renal hemodynamics and function

The biologic action of angiotensin-converting enzyme (ACE) includes conversion of angiotensin 1 to angiotensin II (A II) and degradation of bradykinin. Thus, pharmacologic blockade of ACE is expected to augment endogenous bradykinin activity. A study using a specific bradykinin inhibitor revealed that the activation of bradykinin by an ACE inhibitor has the potential to affect the function of the kidney in several ways. It has been shown in vitro that bradykinin is a highly selective efferent (vs. afferent) arteriolar dilator. An in vivo study using both ACE inhibitors and bradykinin antagonists demonstrated that, through this efferent-arteriolar dilating effect, the bradykinin activated by ACE inhibition causes a profound reduction in glomerular pressure. In contrast, the latter phenomenon is absent during administration of an angiotensin II type 1 (AT1)-receptor antagonist, a finding consistent with the notion that AT1 antagonists are devoid of kininase inhibitory action. Due to this difference, AT1 antagonists appear to be inherently better A II inhibitors than ACE inhibitors where glomerular filtration is concerned. This speculation was verified in an acute experimental setting. It is conceivable, however, that the relatively high glomerular pressure maintained during AT1-antagonist administration may have different effects on the kidney in the long term, because the salutary effect of ACE inhibition to protect kidneys from progressive damage in chronic renal disease is attributed in part to its potent glomerular-pressure-lowering effect. The long-term effects of losartan in the kidney will need to be examined in human studies.